<i>In vivo</i> assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography

High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (µ(raf)) at different skin layers could be assessed.(.) IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased µ(raf) in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative µ(raf) in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high µ(raf) in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV-OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone

Serious adverse events and compensation in registration trials : a review of data from a Japanese university hospital

Background: Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results: Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions: The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials

The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients.

Objective: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. Methods: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. Results: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. Conclusion: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model

Measurement and Analysis of Electromyography for Sequential Mastication

　In the palatability of food, texture is a major factor of food quality. The physical shear force value of meat has been measured. However, quantitative relationship and characterization between shear force value and tenderness as a sensory perception has not been clear. Therefore, a computer system was developed to analyze and to measure the electromyography (EMG) for mastication. 　The integral EMG values were almost constant by sequential mastication up to five times. The average of integral EMG values were 63.6 mV with tender meat of pork fillet and 153.8 mV with firm meat of beef round, giving a ratio of 2.4 times. The shear force values of similar samples were 2,300 g and 8,300 g each, and the ratio was 3.6 times. Sensory texture of the subjective feeling was 3ﾝ4 times that corresponded with the shear force value. The integral EMG value could be thought to compress the amount of texture sense. 　The integral EMG varied greatly in food, and showed lower value in order of boiled fish surimi, steamed fish paste, pork sausage, konnyaku (devil’s tongue), pork fillet, beef loin, pork ham portion, roast beef, pork loin and beef round. Generally this order reflected the sensory texture of chewing. The deviation of the integral EMG value was smaller than expected, so it has a definite possibility for practical use

Lifestyle factors and visible skin aging in a population of Japanese elders.

BACKGROUND: The number of studies that use objective and quantitative methods to evaluate facial skin aging in elderly people is extremely limited, especially in Japan. Therefore, in this cross-sectional study we attempted to characterize the condition of facial skin (hyperpigmentation, pores, texture, and wrinkling) in Japanese adults aged 65 years or older by using objective and quantitative imaging methods. In addition, we aimed to identify lifestyle factors significantly associated with these visible signs of aging. METHODS: The study subjects were 802 community-dwelling Japanese men and women aged at least 65 years and living in the town of Kurabuchi (Takasaki City, Gunma Prefecture, Japan), a mountain community with a population of approximately 4800. The facial skin condition of subjects was assessed quantitatively using a standardized facial imaging system and subsequent computer image analysis. Lifestyle information was collected using a structured questionnaire. The association between skin condition and lifestyle factors was examined using multivariable regression analysis. RESULTS: Among women, the mean values for facial texture, hyperpigmentation, and pores were generally lower than those among age-matched men. There was no significant difference between sexes in the severity of facial wrinkling. Older age was associated with worse skin condition among women only. After adjusting for age, smoking status and topical sun protection were significantly associated with skin condition among both men and women. CONCLUSIONS: Our study revealed significant differences between sexes in the severity of hyperpigmentation, texture, and pores, but not wrinkling. Smoking status and topical sun protection were significantly associated with signs of visible skin aging in this study population

Antibiotic-dependent instability of homeostatic plasticity for growth and environmental load

Reducing antibiotic usage in livestock animals has become an urgent issue worldwide to prevent antimicrobial resistance. Here, abuse of chlortetracycline (CTC), a versatile antibacterial agent, on the performance, blood components, fecal microbiota, and organic acid concentration in calves was investigated. Japanese Black calves were fed milk replacer containing CTC at 10 g/kg (CON) or 0 g/kg (EXP). Growth performance was not affected by CTC administration. However, CTC administration altered the correlation between fecal organic acids and bacterial genera. Machine learning methods such as association analysis, linear discriminant analysis, and energy landscape analysis revealed that CTC administration affected according to certain rules the population of various types of fecal bacteria. It is particularly interesting that the population of several methane-producing bacteria was high in the CON, and that of Lachnospiraceae, a butyrate-producing bacteria, was high in the EXP at 60 d of age. Furthermore, statistical causal inference based on machine learning data estimated that CTC treatment affects the entire intestinal environment, inhibiting butyrate production for growth and biological defense, which may be attributed to methanogens in feces. Thus, these observations highlight the multiple harmful impacts of antibiotics on intestinal health and the potential production of greenhouse gas in the calves

Involvement of peripheral ionotropic glutamate receptors in orofacial thermal hyperalgesia in rats

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to elucidate the mechanisms that may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) neurons to heat or cold stimulation of the orofacial region following glutamate (Glu) injection.</p> <p>Results</p> <p>Glu application to the tongue or whisker pad skin caused an enhancement of head-withdrawal reflex and extracellular signal-regulated kinase (ERK) phosphorylation in Vc-C2 neurons. Head-withdrawal reflex and ERK phosphorylation were also enhanced following cold stimulation of the tongue but not whisker pad skin in Glu-injected rats, and the head-withdrawal reflex and ERK phosphorylation were enhanced following heat stimulation of the tongue or whisker pad skin. The enhanced head-withdrawal reflex and ERK phosphorylation after heat stimulation of the tongue or whisker pad skin, and those following cold stimulation of the tongue but not whisker pad skin were suppressed following ionotropic glutamate receptor antagonists administration into the tongue or whisker pad skin. Furthermore, intrathecal administration of MEK1/2 inhibitor PD98059 caused significant suppression of enhanced head-withdrawal reflex in Glu-injected rats, heat head-withdrawal reflex in the rats with Glu injection into the tongue or whisker pad skin and cold head-withdrawal reflex in the rats with Glu injection into the tongue.</p> <p>Conclusions</p> <p>The present findings suggest that peripheral Glu receptor mechanisms may contribute to cold hyperalgesia in the tongue but not in the facial skin, and also contribute to heat hyperalgesia in the tongue and facial skin, and that the mitogen-activated protein kinase cascade in Vc-C2 neurons may be involved in these Glu-evoked hyperalgesic effects.</p

Optimal waist circumference cut-off points and ability of different metabolic syndrome criteria for predicting diabetes in Japanese men and women: Japan Epidemiology Collaboration on Occupational Health Study

Abstract Background We sought to establish the optimal waist circumference (WC) cut-off point for predicting diabetes mellitus (DM) and to compare the predictive ability of the metabolic syndrome (MetS) criteria of the Joint Interim Statement (JIS) and the Japanese Committee of the Criteria for MetS (JCCMS) for DM in Japanese. Methods Participants of the Japan Epidemiology Collaboration on Occupational Health Study, who were aged 20–69 years and free of DM at baseline (n = 54,980), were followed-up for a maximum of 6 years. Time-dependent receiver operating characteristic analysis was used to determine the optimal cut-off points of WC for predicting DM. Time-dependent sensitivity, specificity, and positive and negative predictive values for the prediction of DM were compared between the JIS and JCCMS MetS criteria. Results During 234,926 person-years of follow-up, 3180 individuals developed DM. Receiver operating characteristic analysis suggested that the most suitable cut-off point of WC for predicting incident DM was 85 cm for men and 80 cm for women. MetS was associated with 3–4 times increased hazard for developing DM in men and 7–9 times in women. Of the MetS criteria tested, the JIS criteria using our proposed WC cut-off points (85 cm for men and 80 cm for women) had the highest sensitivity (54.5 % for men and 43.5 % for women) for predicting DM. The sensitivity and specificity of the JCCMS MetS criteria were ~37.7 and 98.9 %, respectively. Conclusion Data from the present large cohort of workers suggest that WC cut-offs of 85 cm for men and 80 cm for women may be appropriate for predicting DM for Japanese. The JIS criteria can detect more people who later develop DM than does the JCCMS criteria

Clinical trials for drug approval : a pilot study of the view of doctors at Tokushima University Hospital

The development of new and useful pharmaceutical drugs is essential in order to improve the quality of drug therapeutics. Clinical trials play a central role in drug development. Over time, the clinical trial infrastructure has improved and is now integrating the contribution of clinical research coordinators (CRC). Nevertheless, the attitude of doctors towards clinical trials still favors conventional/historical methodologies. In the present study, we explored the view of doctors towards clinical trials for drug development, in order to improve communication among participants, sponsors, and investigators. A questionnaire was designed for this pilot study. The questionnaire included general attitudes, difficult points, the benefit of doctors in participating as investigators, special attention requirements, and the expected role of CRC in clinical trials for drug approval. In addition, the appropriate use of the outpatient clinic was examined. The questionnaire was provided to doctors in each department of Tokushima University Hospital in 2000 and 2004. Because of the small number of subjects included in this pilot study, no statistical analysis is presented. A total of 89 (81%) and62 (56%) doctors among 110 responded to the survey in 2000 and 2004, respectively. Inquiries about the familiarity of the physicians with clinical trials for drug approval revealed that 84% in 2000 and 66% in 2004 were aware of such trials. The attitude towards participating as investigators in the clinical trials was favorable, with a response of 66% in 2000 and 58% in 2004. Patients’ refusal and the informed consent process were considered difficult areas by many doctors. Expected roles of CRC included activities based on the nurse’s specialty. Although many doctors agreed to take care of the study participants separately from the clinical practice, they lacked the time to do so. In spite of the doctors’ workload reduction by introduction of the CRC concept, their views regarding clinical trials for drug approval remain conventional. Further refinement in the support process by CRC should be considered in our hospital, and the views of the doctors should be investigated in a larger study, in order to promote clinical trials for drug approval in Japan

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov